Mesenchymal Stem Cells Do Not Prevent Antibody Responses against Human alpha-L-Iduronidase when Used to Treat Mucopolysaccharidosis Type I

Mesenchymal Stem Cells Do Not Prevent Antibody Responses against Human alpha-L-Iduronidase when Used to Treat Mucopolysaccharidosis Type I

Author Matsumoto, Priscila Keiko Autor UNIFESP Google Scholar
Stilhano, Roberta Sessa Autor UNIFESP Google Scholar
Samoto, Vivian Yochiko Google Scholar
Takiya, Christina Maeda Google Scholar
Peres, Giovani Bravin Autor UNIFESP Google Scholar
Correa da Silva Michelacci, Yara Maria Autor UNIFESP Google Scholar
Silva, Flavia Helena da Autor UNIFESP Google Scholar
Pereira, Vanessa Goncalves Autor UNIFESP Google Scholar
D'Almeida, Vania Autor UNIFESP Google Scholar
Navarro Marques, Fabio Luiz Google Scholar
Otake, Andreia Hanada Google Scholar
Chammas, Roger Google Scholar
Han, Sang Won Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade Federal do Rio de Janeiro (UFRJ)
Univ Fed Rio Grande do Sul
Universidade de São Paulo (USP)
Canc Inst São Paulo State
Abstract Mucopolysaccharidosis type I (MPSI) is an autosomal recessive disease that leads to systemic lysosomal storage, which is caused by the absence of alpha-L-iduronidase (IDUA). Enzyme replacement therapy is recognized as the best therapeutic option for MPSI; however, high titers of anti-IDUA antibody have frequently been observed. Due to the immunosuppressant properties of MSC, we hypothesized that MSC modified with the IDUA gene would be able to produce IDUA for a long period of time. Sleeping Beauty transposon vectors were used to modify MSC because these are basically less-immunogenic plasmids. for cell transplantation, 4x10(6) MSC-KO-IDUA cells (MSC from KO mice modified with IDUA) were injected into the peritoneum of KO-mice three times over intervals of more than one month. the total IDUA activities from MSC-KO-IDUA before cell transplantation were 9.6, 120 and 179 U for the first, second and third injections, respectively. Only after the second cell transplantation, more than one unit of IDUA activity was detected in the blood of 3 mice for 2 days. After the third cell transplantation, a high titer of anti-IDUA antibody was detected in all of the treated mice. Anti-IDUA antibody response was also detected in C57Bl/6 mice treated with MSC-WT-IDUA. the antibody titers were high and comparable to mice that were immunized by electroporation. MSC-transplanted mice had high levels of TNF-alpha and infiltrates in the renal glomeruli. the spreading of the transplanted MSC into the peritoneum of other organs was confirmed after injection of In-111-labeled MSC. in conclusion, the antibody response against IDUA could not be avoided by MSC. On the contrary, these cells worked as an adjuvant that favored IDUA immunization. Therefore, the humoral immunosuppressant property of MSC is questionable and indicates the danger of using MSC as a source for the production of exogenous proteins to treat monogenic diseases.
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number FAPESP: 08/56529-1
FAPESP: 2008/56530-0
FAPESP: 2009/52235-6
Date 2014-03-18
Published in Plos One. San Francisco: Public Library Science, v. 9, n. 3, 9 p., 2014.
ISSN 1932-6203 (Sherpa/Romeo, impact factor)
Publisher Public Library Science
Extent 9
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000333259900135

Show full item record


Name: WOS000333259900135.pdf
Size: 4.097Mb
Format: PDF
Open file

This item appears in the following Collection(s)




My Account